1. Technical Field
This disclosure relates to reduction of scars associated with healing tissue. More particularly, wounds are treated with an oxidized cross-linked polysaccharide having a chemically induced charge.
2. Background of Related Art
Dextran is a polysaccharide which is produced from sucrose by bacteria belonging to the genera Leuconostoc, Streptococcus and Lactobacillus, all of which belong to the family Lactobacillaceae. The majority of known dextrans are formed by strains of Leuconostoc mesenteroides. A detailed discussion of dextran is provided in the Encyclopedia of Polymer Science and Engineering, Vol. 4, pp. 752 et seq. (1986) (John Wiley and Sons), hereby incorporated by reference. Dextran, in which 1-6 linkages predominate, may be represented as follows: 
Certain dextran derivatives are well known. Dextran which is crosslinked with epichlorohydrin is described in U.S. Pat. No. 3,042,667 and in British Patent No. 1,013,585 and is commercially available under the tradename SEPHADEX from Pharmacia Corp., Piscataway, N.J. Epichlorohydrin (CH2OCHCH2Cl) reacts with the pendant hydroxyl groups on dextran to form ether bound bridges between dextran chains.
Various other derivatives of dextran are known. For example, see U.S. Pat. Nos. 4,963,666, (ester crosslinking), 4,591,638 (ester crosslinking), 2,988,455 (oxidized), 4,370,476 (ferric hydroxide complexes), 4,339,360 (activated oxidized) and 4,308,254 (oxidized support).
Dextran has been employed in the treatment of wounds. For example, an insoluble hydrophilic cross-linked dextran polymer in powder form has been used for the debridement of wounds, i.e., the removal of foreign bodies, pus, exudates and irrevocably damaged and devitalized tissue from tissue wounds. This dextran polymer, which is formed by crosslinking dextran with epichlorohydrin, is applied to heavily exudating wounds, allowed to gel and then washed out. The crosslinked dextran, commercially known as DEBRISAN(copyright), absorbs the exudates, including the components that tend to impede tissue repair. Consequently, this composition promotes wound healing by retarding eschar formation and by keeping lesions soft and pliable.
Dextran derivatives have been used to promote hard tissue growth and repair and soft connective tissue growth and repair in mammals as described in U.S. Pat. Nos. 4,988,358 and 5,092,883, respectively. In one aspect, SEPHADEX, a cross-linked dextran available from Pharmacia Corp., (Piscataway, N.J.), linked with diethylaminoethyl (DEAE) functional groups as a basic anion exchanger is used for promoting soft tissue growth and repair by applying an effective quantity thereof to a site of tissue defect. The chemically induced surface charges promote soft connective tissue formation. In U.S. Pat. No. 5,092,883, examples 4 and 5 indicate that positively charged DEAE-Sephadex beads are associated with stimulation effect on fibroblastic activity and that defects treated with the beads were filled with dense, highly cellular soft connective tissue. Wounds with positively charged beads are shown to be stronger than control wounds. There is, however, no recognition that scarring, which may typically be associated with healing wounds, can be reduced.
A scar is the mark left in the skin or an internal organ by new connective tissue that replaces tissue which has been injured by, e.g., burn, ulcer, abrasion, incision, etc. Scars may be viewed as unsightly defects which can result in psychological discomfort of people bearing such scars. As a result, the search for effective scar reducing measures has been ongoing. For example, as described in International Application No. PCT/GB92/00570, a composition for use in the treatment of wounds to inhibit scar tissue formation includes an activity-inhibiting amount of a growth factor neutralizing agent. It is therein indicated that TGF-xcex2 appears to be highly active in connection with organization of collagen leading to the formation of scar tissue. In accordance with PCT/GB92/00570, scar tissue formation is reduced by neutralizing TGF-xcex2.
A method of reducing scar formation at a wound site includes contacting the wound site with an effective scar reducing amount of a cross-linked polysaccharide having a positive charge and thereby reducing scar formation as the wound site heals. Such polysaccharide include bioabsorbable cross-linked dextrans or alginates. The positive charge may be provided by diethylaminoethyl (DEAE) moieties. The cross-linked polysaccharide can be applied to the wound site as a powder or bead. The cross-linked polysaccharide may also be contained in a composition including a pharmaceutically acceptable vehicle. Biocompatable surgical devices provided with an effective scar reducing amount of a cross-linked polysaccharide having a positive charge reduce scar formation at healing wound sites.
A method of reducing the activity of the TGF-xcex2 includes applying an effective TGF-xcex2 activity reducing amount of a cross-linked polysaccharide having a positive change to a locus having TFG-xcex2 activity.